EFFECTS OF MINERAL FIBERS ON THE EXPRESSION OF GENES WHOSE PRODUCT MAY PLAY A ROLE IN FIBER PATHOGENESIS

To determine which factors are useful for the risk assessment of man-m ade fibers, we examined the gene expression of proinflammatory cytokin es, growth factors, manganese superoxide dismutase (MnSOD), and induci ble nitric oxide synthase (iNOS) in mineral fiber-exposed rats by mean s of reverse transcription-polymerase chain reaction (RT-PCR). Male Wi star rats received a single intratracheal instillation of either salin e (control) or two types of fibers (2 mg of Union Internationale Centr e le Cancer (UICC) chrysotile or alumina silicate refractory ceramic f iber [RCF]). Expression of interleukin-1 alpha (IL-1 alpha), interleuk in-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), platelet-derivin g growth factor-A, (PDGF-A), platelet-deriving growth factor-B (PDGF-B ), transforming growth factor beta 1 (TGF-beta 1), basic fibroblast gr owth factor (bFGF), MnSOD, and iNOS mRNA from lung and lipopolysacchar ide (LPS)-stimulated alveolar macrophages (AM) were assessed by RT-PCR . Among these factors, IL-1 alpha, TNF-alpha, IL-6, bFGF: and iNOS wou ld be the possible parameters for the risk assessment of fibers. In a follow-up study, we investigated the time course (3 days, 1 week, 1 mo nth, and 3 months) of expression of IL-1 alpha and TNF-alpha by LPS-st imulated AM exposed to mineral fibers in vivo. Male Wistar rats were i nstilled intratracheally with saline or fibers (2 mg of Union Internat ionale Contre le Cancer UICC crocidolite or potassium octatitanate whi sker [TW]). The expression of IL-1 alpha mRNA by fibers was greatest i n TW, crocidolite, chrysotile, and RCF-instilled rat AM, in that order . The increase of IL-1 alpha and TNF-alpha mRNA in AM peaked at 1 mont h and 3 days after exposure to crocidolite or TW, respectively. The ex pression of IL-1 alpha by fibers (crocidolite, chrysotile, TW, and RCF ) may be a good indicator of the pathologic potential of fibers.